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March 1998 - Papers of the Month
1. Adolph R, et al. Cellular content and permeability of
intraluminal thrombus in AAA. J Vasc Surg 1997;25:916-
26.
Purpose - "...the precise role of the intraluminal
thrombus in the formation, enlargement, and rupture of
AAA is unknown."
Methods - "Tests performed were light, transmission, and
scanning electron microscopy; fluid permeability
measurements; and Western blots."
Results - The thrombus "is structurally complex and is
traversed...by a continuous network of interconnected
canaliculi." There is "cellular penetration for at least
1 cm from the luminal surface of the thrombus." "Fibrin
degradation occurred principally at the abluminal
surface."
Comment by mdt: David Vorp at the Univ Pittsburgh and
his colleagues are the first group to show much interest
in recent years in this interesting feature of the AAA,
namely its rather constant feature of intraluminal
thrombus. Ever since Eugene Bernstein and colleagues
reported that the extent of thrombus had a correlation
with the rate of enlargement, it has seemed clear that
the role of the thrombus deserved closer attention.
Jessie Jean-Claude, first author of a paper from our
laboratory, reported that plasmin is elevated in soluble
extracts of AAA tissue. Vorp and colleagues report that
fibrin degradation is most intense in the thrombus
adjacent to the aortic wall. Since plasmin is an
activator of the MMP's (which we and others have shown to
be important mediators of aortic matrix destruction), it
is possible that clot correlates with rate of aneurysm
enlargement due to permeation of the aortic wall with
plasmin from the thrombus.
2. Boyle JR, et al. Doxycycline inhibits elastin
degradation and reduces metalloproteinase activity in a
model of aneurysm disease. J Vasc Surg 1998; 27: 354-
61.
Purpose - "The ability of doxycycline - an MMP inhibitor
- to reduce matrix degradation was assessed in a ...
model of aneurysmal disease that used a brief pulse of
elastase to induce MMP production and elastin degradation
in arterial organ culture."
Methods - "Porcine aortic segments were incubated in
exogenous pancreatic elastase for 24 hours before culture
... for 13 days with both 1 and 10 mg/L doxycycline."
Results - "... a significant preservation of elastin in
aorta treated with doxycycline 10 mg/L (p<0.001)."
"...this preservation was accompanied by a significant
reduction in MMP-9 activity."
Comment by mdt: This interesting paper is nicely
illustrated and presented. The results confirm a
previous study from the Washington Univ (St. Louis)
group, which used the Anidjar/Dobrin elastase infusion
model in the rat. Because of increased awareness of the
importance of screening for AAA disease in our aging
population, especially among those who have a family
history, pharmacological approaches to the stabilization
of small AAA's are becoming increasingly interesting.